Birth defects affect about one in every 33 babies born in the United States each year. They are the leading cause of infant deaths, accounting for more than 20% of all infant deaths. Babies born with birth defects have a greater chance of illness and long term disability than babies without birth defects. The neurofibromatoses are genetic disorders that cause tumors to grow in the nervous system. The tumors begin in the supporting cells that make up the nerves and the myelin sheath--the thin membrane that envelops and protects the nerves. These disorders cause tumors to grow on nerves and produce other abnormalities such as skin changes and bone deformities. Although many affected persons inherit the disorder, between 30 and 50 percent of new cases arise spontaneously through mutation (change) in an individual's genes. Once this change has taken place, the mutant gene can be passed on to succeeding generations. Scientists have classified the disorders as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis, a type that was once considered to be a variation of NF2. NF1 is the more common type of the neurofibromatoses. In diagnosing NF1, a physician looks for changes in skin appearance, tumors, or bone abnormalities, and/or a parent, sibling, or child with NF1. Symptoms of NF1, which may be evident at birth and nearly always by the time the child is 10 years old, may include light brown spots on the ski ("cafe-au-lait" spots), two or more growths on the iris of the eye, a tumor on the optic nerve, a larger than normal head circumference, and abnormal development of the spine, a skull bone, or the tibia. NF2 is less common and is characterized by slow-growing tumors on the eighth cranial nerves. The tumors cause pressure damage to neighboring nerves. To determine whether an individual has NF2, a physician looks for eighth nerve tumors, cataracts at an early age or changes in the retina that may affect vision, other nervous system tumors and similar signs and symptoms in a parent, sibling, or child. The distinctive feature of schwannomatosis is the development of multiple schwannomas (tumors made up of certain cells) everywhere in the body except on the vestibular branch of the 8th cranial nerve. The dominant symptom is pain, which develops as a schwannoma enlarges or compresses nerves or adjacent tissue. Some people may develop numbness, tingling, or weakness in the fingers and toes Treatment Surgery is often recommended to remove the tumors. Some NF1 tumors may become cancerous, and treatment may include surgery, radiation, or chemotherapy. Surgery, radiation, and chemotherapy also may be used to control or reduce the size of optic nerve tumors when vision is threatened. Some bone malformations can be corrected surgically For NF2, improved diagnostic technologies, such as MRI, can reveal tumors as small as a few millimeters in diameter, thus allowing early treatment. Surgery to remove tumors completely is one option but may result in hearing loss. Surgery also can correct cataracts and retinal abnormalities. There is no currently accepted medical treatment or drug for schwanomatosis, but surgical management is often effective. Pain usually subsides when tumors are removed completely. Genetic testing is available for families with documented cases of NF1 and NF2 but such testing for schwannomatosis currently does not exist. Prognosis In most cases, symptoms of NF1 are mild, and individuals live normal and productive lives. In some cases, however, NF1 can be severely debilitating and may cause cosmetic and psychological issues. The course of NF2 varies greatly among individuals. In some cases of NF2, the damage to nearby vital structures, such as other cranial nerves and the brain stem, can be life-threatening. Most individuals with schwannomatosis have significant pain. In some extreme cases the pain will be severe and disabling. I Have NF (Video on Demand) Neurofibromatosis: A Handbook for Patients, Families and Health Care Professionals Research Being Done Several years ago, research teams located the exact position of the NF1 gene on chromosome 17. The product of the NF1 gene is a large and complex protein called neurofibromin, which is primarily active in nervous cells as a regulator of cell division. Intensive efforts have let to the identification of the NF2 gene on chromosome 22. The NF2 gene product is a tumor-suppressor protein called merlin. Ongoing research continues to discover additional genes that appear to play a role in NF-related tumor suppression or growth. Other research is aimed at understanding how the genetic mutations that cause the benign tumors of NF1 also cause nerve cells and nerve networks to form abnormally during fetal development, which later result in the learning disabilities and cognitive deficits of children with the disorder. Additional research is aimed at understanding the natural history of tumors in NF2 and determining possible factors that may regular their growth patterns. The Interinstitute Medical Genetics Research Program at the NIH Clinical Center conducts NF2 family history research. Using specimens from some of the families, scientists have isolated and sequenced the NF2 gene and have described two different patterns of clinical features in NF2 patients. Investigators are continuing to study these patterns to see if they correspond to specific types of gene mutations. Recap CDC scientists reviewed population-based epidemiologic information on the NF1 gene and neurofibromatosis 1. Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is caused by mutations of the NF1 gene, which is located at chromosome 17q11.2. A wide variety of NF1 mutations have been found in patients with NF1. No frequently recurring mutation has been identified. Diagnosis of NF1 is based on established clinical criteria. Average life expectancy of patients with NF1 is probably reduced by at least 10 to 15 years, with malignancy as the most common cause of death. Substantial variability in expression of NF1 features occurs, even in affected members of a single family. Laboratory testing for NF1 mutations is difficult. A protein truncation test is commercially available, but its sensitivity, specificity, and predictive value have not been established. The prevalence of clinically diagnosed NF1 ranges from 1/2,000 to 1/5,000 in most population-based studies.